The main objective of this proposal is to carry out a series of experiments in dogs with end-to-side portacaval shunt in order to shed some light on the role of tyrosine metabolism in the etiology of human hepatic encephalopathy and its cardiovascular and hemodynamic implications. For this, we intend to follow the approach underlined below: 1) Studies will be undertaken to obtain evidence concerning morphologic and functional changes resulting in the liver after the production of hepatic encephalopathy in dogs with end-to-side portacaval shunt. Cardiovascular and hemodynamic consequences of hepatic coma will also be investigated by evaluation of systemic arterial pressure, cardiac output, creatinine clearance and renal blood flow in these dogs. 2) Metabolic studies in vivo: In order to identify specific blocks in degradation of tyrosine, a detailed study of the metabolism of tyrosine-3H will be carried out in control and shunted dogs. Here, the 3 metabolic routes for tyrosine metabolism will be investigated (tyrosine aminotransferase, tyrosine hydroxylase and tyrosine decarboxylase) by examining the kinetics of the production of 4-hydroxyphenylpyruvic acid, tyramine and L-dopa. The importance of hepatic monoamine oxidase activity in the detoxification of biogenic amines will be determined by studying the disposition of tyramine-3H in pre- and post-shunted dogs. Any changes in brain catecholamines turnover in hepatic coma will be evaluated by studying the cerebral and peripheral disposition of dopamine-3H in control and encephalopathic dogs. 3) Studies in vitro: To verify the in vivo studies, the specific activities of enzymes involved in the metabolism of tyrosine will be determined in selected tissue samples of encephalopathic and control dogs. 4) Studies aimed at correcting the problem of hepatic encephalopathy. For this, two approaches will be followed: one based on L-dopa therapy and the other on the administration of specific diets.